Abstract

No deranged presynaptic monoamine metabolism in the brain has been directly demonstrated in mood disorders, in spite of the rich but indirect pharmacological evidence for a decreased efficacy of monoaminergic synaptic transmission in depression, especially as for serotonin. The availability of 11C-labelled 5-hydroxytryptophan (5-HTP) and L-DOPA, the direct precursors in the synthetic pathways to serotonin and dopamine, has allowed positron emission tomographic (PET) studies in 8 healthy volunteers and 6 patients suffering from unipolar depression. Main results indicate (1) decreased uptake of [11C]5-HTP and [11C]L-DOPA over the blood-brain barrier in depression (which is not altered by dietary tryptophan depletion in healthy volunteers), and (2) an increased utilization of [11C]5-HTP (but not [11C]L-DOPA), in the lower region of the medial prefrontal cortex, mainly of the left side. This phenomenon presumably mirrors an increased synthesis of serotonin in this area and might represent a local compensatory increase in a situation of a general serotonergic hypometabolism. Analyses of interactions of both ligands between striatal and prefrontal areas suggest significantly stronger positive correlations in depression than in health, that could be interpreted as a less pronounced autonomy between brain regions in depression.